Full text of some older papers, including most theory papers

Some classical papers

Hill,A.V. (1909) The mode of action of nicotine and curari determined by the
form of the contraction curve and the method of temperature coefficients. J.
Physiol. (Lond), 39, 361-373. [Get pdf (0.58 Mb)] This is A.V. Hill's first paper. It describes the Langmuir
equation (both rates and equilibrium) some time before Langmuir (1918) did so,

Haldane, J.B.S. (1930) Enzymes, Longmans, Green and Co.London. [Get pdf (0.31.Mb)] This is the section of Haldane's book that describes
mechanisms: Michaelis-Menten and Briggs-Haldane, and in particular the case
of competitive inhibition (see pp 46-47 of book, pp 20-21 of pdf
file).

Older papers from DC lab

The JSTOR web site now has in pdf format,
in its General Science Collection, the entire contents of the Royal
Society journals back to the 17th century, Proceedings of the National
Academy of Sciences, and of Science. The pdf files can be downloaded
by any site that subscribes to JSTOR.

Colquhoun, D. & Sakmann, B. (1985). Fast events in single-channel currents
activated by acetylcholine and its analogues at the frog muscle end-plate. Journal
of Physiology ( London ) 369 , 501-557.[Get pdf (7 Mb)]See also the 'classical perspective on this paper, written in 2007 (here).

Colquhoun, D. & Hawkes, A.G. (1982) On the stochastic properties of bursts of
single ion channel openings and of clusters of bursts. Philosophical Transactions
of the Royal Society LondonB 300, 1-59.This is the paper that describes the notation used in all subsequent papers, and uses it to obtain distributions of open and shut times, of burst properties, and the properties of clusters of bursts (it supersedes the 1981 paper)[Get PDF (6 Mb!)]

Colquhoun, D., Dreyer, F., & Sheridan, R. E. (1979). The actions of tubocurarine at the frog neuromuscular junction. Journal of Physiology (London)293, 247-284.This paper describes the very long lasting channel
blockages' that can be produced by (+)-tubocurarine (in addition to its
competitive action). Such long blockages would be hard to identify on single
channel records so even if we had been able to measure them in 1977 -78,
the voltage-jump method used here might still have been the best.[Get PDF (4.3 Mb)]

Colquhoun, D.(1981). How fast do drugs work?
Trends in Pharmacological Sciences8,
212 – 217This old paper is still sometimes found useful by students.
It was written as an introduction to ideas about measuring the rates of reactions,
as opposed to equilibrium constants. It therefore deals with macroscopic responses,
noise analysis and single channels in an elementary way.
[Get pdf]

Colquhoun, D. & Hawkes, A. G. (1977). Relaxation and fluctuations of membrane
currents that flow through drug-operated channels. Proceedings of the Royal
Society London B199, 231-262.
[Get
pdf 3,2 Mb]This 1977 paper is the first of many
papers written with Alan Hawkes. Its origin dates back to 1972 when I wrote
Alan Hawkes to ask how the noise analysis, recently published by Katz & Miledi, could
be generalised to any reaction mechanism. The theory predicted that the
predominant time constant from noise analysis would be longer than the
mean channel open time, for any realistic values of the rate constants.
The physical meaning of this eluded us at first, but after being pressed
by Bernard Katz to explain the result, we realised that it was a result
of channel openings being predicted to not to occur singly, but in bursts.
By the time the paper came out, Neher & Sakmann's 1976 paper had appeared
and we were soon able to test the prediction,

Colquhoun, D.(1970). How long does a molecule stay on the
receptor? Explanation of a paradox. British Journal of Pharmacology39,
215PThis is the abstract of a talk given at the 1969 meeting
of the British Pharmacological Society. At the time I had just discovered,
via Alan Hawkes, the waiting time paradox. This resolved, at a stroke, many
of the problems that I'd been having in thinking about what happened at the
level of a single drug-receptor complex.
[Get PDF]

Two older papers from books

These two papers have been scanned (because the books in which they appeared
are now hard to find).

Colquhoun, D. (1973). The relation between classical and cooperative models
for drug action. In Drug Receptors, ed. Rang, H. P., pp. 149-182.
Macmillan Press, London.
[get pdf file: 4.04 Mb] This paper attempted to reconcile the emerging knowledge
of cooperativity in ion channel receptors with the more classical views.
It showed that the Schild approach for competitive antagonsists was indeed
valid for a wide range of receptor mechanisms, but that agonists could give
results that were incompatible with Stephenson's ideas. But it failed to
grasp completely the fatal error in the classical approach.

Colquhoun, D. (1987). Affinity, efficacy and receptor classification: is the
classical theory still useful? In Perspectives on hormone receptor classification,
ed. Black, J. W., pp. 103-114. Alan R. Liss Inc., New York.
[get
pdf file: 2.35 Mb]This paper explains why Stephenson's quantitative
formulation contained an error, and how this error implied that none of the
published methods for experimental determination of 'affinity' and 'efficacy'
could actually achieve the separation of these quantities that had been claimed
for them.

Colquhoun, D. & Sheridan, R. E. (1981). The modes of action of gallamine. Proceedings of the Royal Society London B211, 181-203.

Colquhoun, D. & Hawkes, A. G. (1981). On the stochastic properties of single ion channels. Proceedings of the Royal Society London B211, 205-235.(Note -this paper is superseded by the 1982 version (top of page)

Ogden, D. C. & Colquhoun, D. (1985). Ion channel block by acetylcholine, carbachol
and suberyldicholine at the frog neuromuscular junction. Proceedings of the
Royal Society London B 225, 329-355.
[Get pdf] This paper has two appendices of general interest. Appendix
1 gives algebraic reults for the area under a Lorentzian spectral density function
that has been filtered with an 8-pole Butterworth filter. Appendix 2 uses the
theory of clusters of bursts (C& H 1982) to analyse the effects of ion channel
blockers that are not selective for the open state.

Colquhoun, D. and Ogden, D.C. (1988). Activation of ion channels in the frog
end-plate by high concentrations of acetylcholine. Journal of Physiology, 395,
131-159.
[get pdf]

Hawkes, A. G., Jalali, A. & Colquhoun, D. (1990). The distributions of the
apparent open times and shut times in a single channel record when brief events
can not be detected. Philosophical Transactions of the Royal Society London A332, 511-538. [Get PDF]

Colquhoun, D. & Hawkes, A. G. (1990). Stochastic properties of ion channel openings and bursts in a membrane patch that contains two channels: evidence concerning the number of channels present when a record containing only single openings is observed. Proceedings of the Royal Society London B 240, 453-477.

Hawkes, A. G., Jalali, A. & Colquhoun, D. (1992). Asymptotic distributions of apparent open times and shut times in a single channel record allowing for the omission of brief events. Philosophical Transactions of the Royal Society London B337, 383-404. [Get PDF]

Colquhoun, D., Hawkes, A. G. & Srodzinski, K. (1996). Joint distributions of apparent open times and shut times of single ion channels and the maximum likelihood fitting of mechanisms. Philosophical Transactions of the Royal Society London A354, 2555-2590.